EP0987033A1 - Resorbierbares, verformbares Implantationsmaterial - Google Patents

Resorbierbares, verformbares Implantationsmaterial Download PDF

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Publication number
EP0987033A1
EP0987033A1 EP99117914A EP99117914A EP0987033A1 EP 0987033 A1 EP0987033 A1 EP 0987033A1 EP 99117914 A EP99117914 A EP 99117914A EP 99117914 A EP99117914 A EP 99117914A EP 0987033 A1 EP0987033 A1 EP 0987033A1
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EP
European Patent Office
Prior art keywords
biodegradable
deformation
bioabsorbable
implant material
shape
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Granted
Application number
EP99117914A
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English (en)
French (fr)
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EP0987033B1 (de
Inventor
Yasuo Shikinami
Masaki Okuno
Hiroshi Morii
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Takiron Co Ltd
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Takiron Co Ltd
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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C43/00—Compression moulding, i.e. applying external pressure to flow the moulding material; Apparatus therefor
    • B29C43/003—Compression moulding, i.e. applying external pressure to flow the moulding material; Apparatus therefor characterised by the choice of material
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
    • A61B17/56—Surgical instruments or methods for treatment of bones or joints; Devices specially adapted therefor
    • A61B17/58—Surgical instruments or methods for treatment of bones or joints; Devices specially adapted therefor for osteosynthesis, e.g. bone plates, screws, setting implements or the like
    • A61B17/68—Internal fixation devices, including fasteners and spinal fixators, even if a part thereof projects from the skin
    • A61B17/80—Cortical plates, i.e. bone plates; Instruments for holding or positioning cortical plates, or for compressing bones attached to cortical plates
    • A61B17/8085—Cortical plates, i.e. bone plates; Instruments for holding or positioning cortical plates, or for compressing bones attached to cortical plates with pliable or malleable elements or having a mesh-like structure, e.g. small strips
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C43/00—Compression moulding, i.e. applying external pressure to flow the moulding material; Apparatus therefor
    • B29C43/02—Compression moulding, i.e. applying external pressure to flow the moulding material; Apparatus therefor of articles of definite length, i.e. discrete articles
    • B29C43/16—Forging
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29K—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES B29B, B29C OR B29D, RELATING TO MOULDING MATERIALS OR TO MATERIALS FOR MOULDS, REINFORCEMENTS, FILLERS OR PREFORMED PARTS, e.g. INSERTS
    • B29K2995/00—Properties of moulding materials, reinforcements, fillers, preformed parts or moulds
    • B29K2995/0037—Other properties
    • B29K2995/0041—Crystalline
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29K—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES B29B, B29C OR B29D, RELATING TO MOULDING MATERIALS OR TO MATERIALS FOR MOULDS, REINFORCEMENTS, FILLERS OR PREFORMED PARTS, e.g. INSERTS
    • B29K2995/00—Properties of moulding materials, reinforcements, fillers, preformed parts or moulds
    • B29K2995/0037—Other properties
    • B29K2995/005—Oriented
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29K—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES B29B, B29C OR B29D, RELATING TO MOULDING MATERIALS OR TO MATERIALS FOR MOULDS, REINFORCEMENTS, FILLERS OR PREFORMED PARTS, e.g. INSERTS
    • B29K2995/00—Properties of moulding materials, reinforcements, fillers, preformed parts or moulds
    • B29K2995/0037—Other properties
    • B29K2995/0087—Wear resistance
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29L—INDEXING SCHEME ASSOCIATED WITH SUBCLASS B29C, RELATING TO PARTICULAR ARTICLES
    • B29L2031/00—Other particular articles
    • B29L2031/753—Medical equipment; Accessories therefor
    • B29L2031/7532—Artificial members, protheses
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T428/00—Stock material or miscellaneous articles
    • Y10T428/24—Structurally defined web or sheet [e.g., overall dimension, etc.]
    • Y10T428/24273—Structurally defined web or sheet [e.g., overall dimension, etc.] including aperture

Definitions

  • This invention relates to a convenient biodegradable and bioabsorbable implant material which is a biomaterial having high mechanical strength and less mechanical anisotropy, can easily be deformed by bending and/or twisting within ordinary temperature range, has an ability to fix and keep its shape after the deformation as such and can be adjusted into a shape adapted to the surface shape of the region to be applied in the living body in using as such devices of plates, pins and wires.
  • implant materials there are various types of implant materials to be implanted in the living body; for example, devices such as plates, pins and wires made of metals or ceramics are frequently used in the case of osteosynthesis.
  • these implant materials have a problem of reducing strength of peripheral bones due to a stress reducing phenomenon after healing and are excessive shielding strength.
  • implant materials made of metals they have problems in that elution of metal ions may exert bad influences upon the living body, sometimes causing a danger of generating carcinogenicity and that, when they are left in the living body for a prolonged period of time after completion of their role such as osteosynthesis, they inhibit natural growth of bones so that it is suitable to carry out re-operation to take out the implant devices from the living body at an early stage after healing such as of bone fracture.
  • biodegradable and bioabsorbable implant materials and devices for osteosynthesis which are molded with a polyglycolic, a polylactic acid or a copolymer thereof have been developed.
  • Such materials for osteosynthesis particularly the materials for osteosynthesis made of a polylactic acid, are biocompatible because of their good affinity for the alive body and have a favorable property in that they are gradually hydrolyzed in the living body by the contact with body fluids and finally absorbed by the living body, so that they are frequently used in recent years.
  • it is not necessary to remove them by re-operation which is different from the case of the implant devices made of metals.
  • a mini-plate material, etc. made of titanium for use in oral and maxillofacial surgery and brain surgery has an advantage in that it can be used by freely deforming its shape during operation to exert sufficient fixing ability by closely adjusting it to the shape of bone to be treated. Accordingly, in many cases, the same characteristics, i.e., bend-deforming the devices to conform to the shape of the bone upon use, is also in demand for implant devices such as plates for osteosynthesis molded with polylactic acid.
  • a material prepared to have a flat type shape may be used as such in some cases.
  • Such a plate can be used in the scene of operation by thermoforming it at a temperature of approximately from 60 to 80°C to adjust it to the shape of the surface of bone to be treated. Although it is a practical method which uses conventional knowledge on the thermoorming of plastics, it requires complex handling.
  • a molding of polylactic acid having a flat shape such as plate can be easily deformed by bending at ordinary temperature when the thickness is thin.
  • its bending deformation is carried out at an ordinary temperature which is lower than its glass transition point (Tg)
  • Tg glass transition point
  • whitening occurs in the bending-deformed part portion due to change of the morphology and its strength is reduced, thus causing a problem in that it cannot be used as a plate for osteosynthesis.
  • its bending deformation has to be made by heating and softening it as described in the foregoing.
  • the present invention was accomplished by taking the aforementioned problems into consideration.
  • the object of the present invention is to provide a biodegradable and bioabsorbable implant devices which have basically large mechanical strength, can be deformed by bending or twisting within ordinary temperature range and can fix and keep the resulting shape as such, has substantially no anisotropy of strength, can be subjected to repeated deformation of exceeding 20 times (can withstand repeated deformation of more than several hundred times in the case of a wire having a circular section) because of its ability of not easily causing whitening and reduced strength by its deformation in any direction partially due to the change of morphology, and also can give a property to bond to bones within a short period of time as well as a bone conductivity.
  • the biodegradable and bioabsorbable implant material according to the first embodiment of the present invention is characterized in that it comprises a biodegradable and bioabsorbable crystalline polymer capable of effecting deformation such as bending or twisting within ordinary temperature range and having a shape-keeping ability to fix and maintain the shape after deformation as such, wherein molecular chains, domains of molecular chain assembly or crystals of the biodegradable and bioabsorbable polymer are oriented along a large number of reference axes having different axial directions, or clusters having these reference axes having different orientation are assembled in a large number.
  • orientation along a large number of reference axes having different axial directions or “assembly of clusters having reference axes of different orientation” means a multi-axial orientation or an oriented form as the assembly of multi-axially oriented clusters, so that its meaning is completely different from that of no orientation which means no oriented form (so-called randomly oriented form having no orientation treatment).
  • ordinary temperature range means a temperature range of from 0°C or more to less than 50°C.
  • the biodegradable and bioabsorbable implant material according to the second embodiment of the present invention is the implant material as set forth in the first embodiment, wherein it is obtained by forging a billet comprising a biodegradable and bioabsorbable crystalline polymer at a low temperature between Tg and Tc (Tg: glass transition temperature; Tc: crystallization temperature) and then forging it at the temperature by changing its mechanical direction (MD) (which may be carried out a plurality of times), and the biodegradable and bioabsorbable implant material according to third embodiment of the present invention uses a crystalline polylactic acid as the biodegradable and bioabsorbable crystalline polymer.
  • Tg glass transition temperature
  • Tc crystallization temperature
  • the biodegradable and bioabsorbable implant material according to the fouth embodiment of the present invention is an implant device for osteosynthesis use which is formed into a flat heteromorphic shape such as a sheet, a plate, a plate having screw-inserting hole(s), a washer, a button, a mesh or a ribbon
  • the biodegradable and bioabsorbable implant material according to the fifth embodiment of the present invention is an implant device which is formed into a cylindrical shape such as a wire, a cable prepared by making up thin wires into a bundle and twisting the bundle, a rod or a pin
  • the biodegradable and bioabsorbable implant material according to the sixth embodiment of the present invention is characterized in that it further contains a bioceramics powder.
  • the "billet" of the second embodiment of the present invention is not limited to a round bar and its shape is not limited, so that it maybe a polygonal prism having different number of angles.
  • the seventh embodiment of the present invention is a biodegradable and bioabsorbable implant material wherein the state of orientation of molecular chains, domains of molecular chain assembly or crystals of the biodegradable and bioabsorbable polymer partially changes by the deformation within ordinary temperature.
  • the shape-adjusting method of eight embodiment of the present invention is characterized in that the biodegradable and bioabsorbable implant material as set forth in any one of the aforementioned first to seventh ebodiments of the present invention is subjected to bending deformation and/or torsional deformation within ordinary temperature range and then the shape after deformation is fixed and kept as such.
  • a crystalline plastic having a glass transition point (Tg) of lower than the usual room temperature (from 25 to 30°C) generally has a morphological phase structure comprising a crystal phase and a rubber phase at room temperature. Because of the presence of rubber layer, the shape after its bending within ordinary temperature range can hardly be kept and fixed and is restored by its elasticity.
  • Polyethylene (Tg: -20°C) and polypropylene (Tg: -10°C) are its familiar examples, and when they are deformed within the ordinary temperature range defined by the present invention and then the external force is removed, they are restored to the original shape or a shape close to the original shape by the rubber elasticity.
  • a crystalline polylactic acid or the like as a typical example of the biodegradable and bioabsorbable polymer to be used in the present invention has a glass transition point (Tg) of higher than the ordinary temperature range (60 to 65°C), shows a phase structure mainly comprising a crystal phase and a glass phase within the ordinary temperature range and contains substantially no rubber phase even when the crystallinity is at least 5% or more, so that its shape after bending deformation within the ordinary temperature range can be kept and fixed as such.
  • Tg glass transition point
  • the aforementioned polymer such as polylactic acid is an assembled body in view of material morphology in which molecular chains, domains of molecular chain assembly or crystals of the polymer are oriented along a large number of reference axes having randomly different axial directions (that is, expression of three-dimensional orientation of a plurality of axial directions is found statistically) or clusters having reference axes having randomly different orientation are assembled in a large number, so that such a deformation property capable of keeping and fixing its shape after bending or twisting treatment is expressed by the generation of mutual "shearing" between surfaces of these assembled masses.
  • a crystalline poly-L-lactic acid as an L-isomer homopolymer and an crystalline poly-D-lactic acid as a D-isomer homopolymer are basically composed of a crystal phase and a glass phase, but a poly-D/L-lactic acid as a copolymer of D-isomer and L-isomer keeps back a crystal phase when the molar ratio of any one of the D-isomer and L-isomer exceeds 80% (88% according to a certain literature) and, when the ratio is 80% or less, the crystal phase mostly disappears and the polymer becomes basically glassy.
  • a copolymer having a D-isomer/L-isomer molar ratio of approximately 80/20 or more or approximately 20/80 or less and a remaining crystallinity of approximately 5% or more it is desirable to use a copolymer having a D-isomer/L-isomer molar ratio of approximately 80/20 or more or approximately 20/80 or less and a remaining crystallinity of approximately 5% or more.
  • the Tg value of such a poly-D/L-lactic acid having a crystallinity of 5% or more and the Tg values of the aforementioned poly-L-lactic acid poly-D-lactic acid are higher than 50°C which is the upper limit of the "ordinary temperature range" of the present invention.
  • the present invention relates to a material having a characteristics that it is freely deformed and fixed at a temperature which is equal to or less than its Tg value and also relates to a deformation method thereof.
  • the ordinary temperature range effective for deformation and fixing is employed as a particular characteristic of the present invention.
  • the forging is effected at a temperature of approximately from 70 to 130°C which is considerably higher than the ordinary temperature but fairly lower than the usual thermoforming temperature. Therefore, when the implant material is deformed within the ordinary temperature range and embedded in the living body, the crystal phase which does not melt at ordinary temperature behaves as a back up structure phase at the time of deformation (the temperature Tm at which the crystal phase melts is about 180°C which is fairly high). Accordingly, the shape after deformation is maintained as such and does not remember to its original shape by the body temperature.
  • restoration of the original shape through disappearance of the orientation requires a temperature rising at least to a level of the forging-treated temperature or more, but the forging temperature is within the range of from 70 to 130°C, which is fairly higher than the body temperature as described in the above, so that it does not remember to its original shape.
  • Such a feature is far superior to that of a titanium plate which has ductility and toughness and can easily be deformed at the site of surgical operation.
  • the implant material of the present invention is subjected to bending deformation and/or torsional deformation within ordinary temperature range and the shape after deformation is fixed and kept as such, as in the case of the shape-adjusting method of the seventh embodiment of the present invention, decisive reduction of strength does not occur so that the implant device can be embedded in the living body by easily adjusting its shape during the operation.
  • Such an excellent mechanical property cannot at all be obtained by the conventional biodegradable and bioabsorbable implant material without orientation or with uniaxial orientation. This is also an essential characteristic when a hereromorphic plate which will be shown later by drawings is used by its deformation.
  • the aforementioned biodegradable and bioabsorbable implant material is formed, for example, into an implant device for osteosynthesis use, having a flat heteromorphic shape such as a sheet, a plate, a plate having screw-inserting hole(s), a washer, a button, a mesh or a ribbon, as in the case of fourth embodiment of the present invention, and used for the bone healing at the site of operation by adjusting its shape to the irregular surface shape of bones through its bending deformation or torsional deformation within the ordinary temperature range.
  • Such an implant material for osteosynthesis use may be a material in which a flat plate is slightly bent or twisted in advance to a predetermined shape.
  • the fifth embodiment of the present invention is also formed into a round or square cylindrical shape such as a wire, a cable prepared by making up thin wires into a bundle and twisting the bundle, a rod or a pin and used at the site of operation, for example, by twist-deforming it as a wire for bone healing or bend-deforming it in response to the bending degree of bones to be healed.
  • the bioceramics powder when included as in the case of the implant material of the sixth embodiment of the present invention, the bioceramics powder exerts an action to deposit and form calcium phosphate existing in the living body on the surface layer of the implant material, so that the implant device binds to the device bone within a relatively short period of time. In consequence, loosening hardly occurs and the fractured bones can be fixed securely. It also expresses a property to conduct formation of new bone to a lost bone region which is formed when the said implant devicce is embedded. It is further effective, because the implant material as a whole is absorbed in the living body and finally disappears at a relatively early stage replaced by the biological bone.
  • FIG. 1A to 1F is an illustration showing plan view of a biodegradable and bioabsorbable implant device for osteosynthesis use, in which 1A is a straight type material, 1B is an L type, 1C is a T type, 1D is a Y type, 1E is a C type and 1F is a straight type having no "necking", and 1G in the drawing is an illustration snowing plan view of a ribbon-shaped bone healing and fixing material for plastic surgery use.
  • Each type of the implant material is formed into a plate shape of approximately from 0.5 to 3.5 mm in thickness having a plurality of screw insertion hole 1, which can be deformed by its bending or twisting within ordinary temperature range (0°C or more and less than 50°C) and has a function to fix and keep its shape after deformation.
  • the thickness is thinner than 0.5 mm, its strength as a plate for osteosynthesis use may become insufficient.
  • the thickness is larger than 2.0 mm, a prolonged period of time is required until its complete degradation and disappearance of tactile perception (3 years or more) so that it can hardly be used in the field of oral surgery.
  • it may have a round or square cylindrical shape such as a wire, a cable prepared by twisting the wires, a rod or a pin.
  • a cylindrical material having, for example, a diameter of from 0.5 to 4.0 mm and a length of from 10 to 30 cm is used, which can be bent, twisted or deformed for example for ligation and is applicable to materials for osteosynthesis use (e.g., pins, wires and the like).
  • It also can be formed into a thin band shape such as a sheet-like ribbon, and such a ribbon has a thickness of from 0.2 to 2.0 mm and a length of from 10 to 30 cm and can be bent, twisted or deformed for example for ligation.
  • these implant devices comprise a biodegradable and bioabsorbable crystalline thermoplastic polymer having a glass transition point (Tg) of higher than room temperature, they have a phase structure basically composed of a crystal phase and a glass phase and their crystallinity is 5% or more.
  • Tg glass transition point
  • the upper limit of the crystallinity does not exceed 70%, because a large number of fine pieces of crystals are formed simultaneously with the degradation of the implant materials as their degradation progresses. Since the amount of the thus formed fine pieces of crystals far exceeds the phagocitosing capacity of macrophages, there is a possibility of causing damage upon peripheral cells and thereby generating inflammation.
  • the material comprises a multi-axially oriented form in which molecular chains, domains of molecular chain assembly or crystals of the biodegradable and bioabsorbable polymer are oriented along many reference axes having random axial directions, or an assembled mass in which clusters having reference axes of randomly different orientation are assembled in a large number.
  • these implant materials are practical because, as described in the foregoing, they have substantially no mechanical anisotropy, are not easily broken when bending-deformed in any direction within the ordinary temperature range which is different from the case of a non-oriented or single direction-oriented implant material, shows very little reduction of strength (deterioration) by repeated bending and maintains about 80% or more of the initial bending strength after repeated bending deformation of exceeding 20 times, so that the strength is hardly reduced after several times of deformation at ordinary temperature during operation. Also, in the case of a wire having circular section, it is not broken after 800 times of repeated bending at an upward/downward angle of 15° as will be shown later in Example 3. While a kirschner wire is broken by about 400 times of bending, this wire has such a durability that its initial strength can be maintained during 800 times of bending.
  • the aforementioned implant materials can be produced by preparing a billet from a biodegradable and bioabsorbable crystalline polymer, forging the billet at a low temperature (glass transition temperature or more and less than crystallizing temperature, preferably from 70 to 130°C, more preferably from 90 to 110°C), further forging at a low temperature by changing its mechanical direction (MD) to make a plate- or rod-shaped multi-axially oriented body or an assembly of oriented clusters, and then cutting it into various flat plate shapes shown in Fig. 1A to 1G while simultaneously carrying out a perforation processing.
  • a wire can be produced by cutting the forged plate-shaped molding into a prismatic shape and processing the prism by removing its corners so that its section becomes circular.
  • the implant material of the present invention can be prepared, for example, by the method described below.
  • a crystallizable biodegradable and bioabsorbable polymer is made into a billet 10 by the known molding method (e.g., the extrusion molding and the injection molding) at a temperature that is higher than the melting point of the polymer and lower than 220°C.
  • the resulting billet 10 is pressed into a small space of the bottom-closed forming mold 20 having a smaller thickness, diameter, etc. than that of the billet 10, while effecting plastic deformation at a low temperature between Tg and Tc, to prepare a forged molding block (plate, billet) 11.
  • the resulting forged molding block 11 is pressed into a small space of the bottom-closed forming mold having a smaller thickness, diameter, etc. than that of the forged molding block 11, while effecting plastic deformation at a low temperature between Tg and Tc, to prepare the molding 1 of the present invention.
  • the forming mold 20 shown in Fig. 2 is an example of the forming molding for preparing a plate-shaped forged molding block 11.
  • the forming molding 20 comprises (1) a mold which comprises a part forming a cavity 21 having a rectangular longitudinal section and having a larger lateral sectional area, in which the billet 10 is filled, a bottomed part forming a cavity 22 having a rectangular longitudinal section and having a smaller lateral sectional area (preferably, about 2/3 to 1/6 of the sectional area of the billet), and the tapered part 23 connecting these two and having a trapezoid longitudinal section, wherein these three parts aligned along the same central axis; and (2) a piston 24 which can be inserted into the cavity 21.
  • the billet 10 filled in the cavity 21 is press-forced into the cavity 22 by continuously or discontinuously applying a pressure, while effecting plastic deformation at a low temperature.
  • the direction of this press-forcing is the mechanical direction MD1.
  • the polymer crystallizes by this forging molding. As shown in Fig. 3A, the crystals of the polymer align in parallel in the directions of a large number of reference axes N that slant toward the axial face M.
  • the axial face M is the mechanical core during the molding, i.e., the area containing the continuous points (lines) at which the forces trout the both sides of the forming mold are concentrated.
  • the crystallized forged molding block 11 as it is or after cutting into an appropriate size is then subjected to the second forging molding by changing the mechanical direction MD (i.e., changing the direction of press-forcing).
  • the forming mold used for the second forging molding may be the similar shape with the above-described forming mold 20.
  • the forming molding comprises (1) a mold which comprises a part forming a cavity having a rectangular longitudinal section and having a larger lateral sectional area (having a smaller laterial sectional area than that of the forged molding block 11), in which the forged molding block 11 is filled, a bottomed part forming a cavity having a rectangular longitudinal section and having a smaller lateral sectional area (preferably, about 2/3 to 1/6 of the sectional area of the forged molding block 11), and the tapered part connecting these two and having a trapezoid longitudinal section, wherein these three parts aligned along the same central axis; and (2) a piston which can be inserted into the cavity.
  • the forged molding block 11 is filled into the cavity of the forming molding in a certain direction so that the press-forcing direction of the second forging molding (MD2) becomes different from the press-forcing direction of the first forging molding (MD1).
  • MD2 is selected to form an angle of 90° against MD1.
  • the forged molding block 11 is press-forced into the cavity continuously or discontinuously, while effecting plastic deformation at low temperature.
  • the crystals of the polymer are oriented along a large number of reference axes having different axial directions, or clusters having these reference axes having different orientation are assembled in a large number.
  • the molecular chains and domains of the molecular chains of the polymer are similarly oriented.
  • the number of total forging moldings is preferably from 2 to 5, more preferably from 2 to 3, because the reference axes along which the crystals orient hardly becomes random and the device obtained can bear to the outer forces such as bending, twisting, etc. in these ranges.
  • the directions of the press-forcing are changed so as to form an angle in the range of preferably from 10° to 170°, more preferably from 45° to 135°, most preferably 90°.
  • Crystalline thermoplastic polymers having a crystallinity of 5% or more which have a glass transition point (Tg) of higher than the upper limit of the ordinary temperature range (50°C) and are hydrolyzed and absorbed in the living body, are used as the biodegradable and bioabsorbable material polymers, among which polylactic acids having an initial viscosity average molecular weight of from 100,000 to 700,000, preferably from 150,000 to 400,000, namely a poly-L-lactic acid, a poly-D-lactic acid and a poly-D/L-lactic acid (provided that it is a copolymer having a D/L molar ratio of approximately 80/20 or more or approximately 20/80 or less and having a crystallinity of 5% or more) are desirable, and these polymers may be used alone or as a mixture of two or more.
  • a biodegradable and bioabsorbable amorphous polymer having a crystallinity of less than 5% shows a certain degree of improvement in strength when it is compressed by forging at a low temperature.
  • a biodegradable and bioabsorbable amorphous polymer having a crystallinity of less than 5% shows a certain degree of improvement in strength when it is compressed by forging at a low temperature.
  • the aforementioned biodegradable and bioabsorbable implant device for osteosynthesis is used at the site of operation for connecting fractured bone parts, by bending and/or twisting it within the ordinary temperature range to deform it into such a shape that it can be fitted to the fractured bone parts and then thrusting fixing screws into the biological bone through the screw insertion hole 1.
  • the implant material of the present invention is markedly convenient, because it does not require a troublesome work of carrying out bending deformation by heating it at about 80°C and its shape can be adjusted easily by bending or torsional deformation at ordinary temperature and because there is no fear of returning to its original shape in the living body.
  • the implant material maintains sufficient strength in the living body during a period of from 1 to 6 months, starting from the commencement of hydrolysis on its surface through its contact with the body fluid until healing of the fractured bone parts, but is finely broken thereafter as its hydrolysis progresses and finally absorbed by the living body and completely disappears. In consequence, it is not necessary to take out the material from the living body by re-operation which is common in the case of conventional metallic implant materials, so that mental and economical burdens on patients can be alleviated.
  • bioceramics powder in the aforementioned plate-shaped implant material for osteosynthesis use, because the bioceramics powder which is present on the surface layer or appeared on the surface by hydrolysis of the polymer allows calcium phosphate or bone tissue in the living body to deposit on or conduct to the surface layer region of the implant material, so that the implant material can bind to the living bone and fix the fractured bone parts securely within a relatively short period of time.
  • bioceramics powder to be used examples include powders of surface-bioactive sintered hydroxyapatite, glass for biological body use of a bioglass or crystallized glass system, biodegradable un-sintered hydroxyapatite (namely, a raw hydroxyapatite which is not treated by sintering or by both sintering or calcination but has a chemical composition similar to that of hydroxyapatite in the living body), dicalcium phosphate, tricalcium phosphate, tetracalcium phosphate, octacalcium phosphate, calcite and diopside, which may be used alone or as a mixed powder of two or more.
  • biodegradable un-sintered hydroxyapatite namely, a raw hydroxyapatite which is not treated by sintering or by both sintering or calcination but has a chemical composition similar to that of hydroxyapatite in the living body
  • dicalcium phosphate tricalcium
  • bioceramics powder at a blending ratio of approximately from 10 to 60% by weight, because the function of bioceramics powder to effect deposition or conduction of calcium phosphate and bone tissue in the living body cannot fully be exerted when the ratio is less than 10% by weight, and the implant material becomes brittle due to reduced toughness when the ratio exceeds 60% by weight.
  • a poly-L-lactic acid (PLLA) having a viscosity average molecular weight of 350,000 was melt-extruded at 190°C to obtain a prismatic billet of 250,000 in viscosity average molecular weight having a rectangular section of 12 mm in length x 50 mm in width.
  • PLLA poly-L-lactic acid
  • This billet was forged at 110°C by press-charging it into the cavity of a forming mold of 7.5 mm in height x 32 mm in width x 60 mm in length, thereby obtaining a molding.
  • This molding was again subjected to the forging molding by changing its mechanical direction (MD) to obtain a plate-shaped multi-axially orientated compression molding of 60 mm in length x 80 mm in width x 3 mm in thickness. Crystallinity of this multi-axially orientated compression molding was calculated to be 43% when measured by a differential scanning colorimeter (DSC).
  • DSC differential scanning colorimeter
  • this multi-axially orientated compression molding was cut out at a direction of 0°, 45° or 90° to prepare a rectangular plate of 30 mm in length x 5 mm in width x 1.5 mm in thickness. Thereafter, its bending strength was measured using an autograph. The results are shown in Table 1. In this connection, temperature at the time of measurement was 22°C (room temperature).
  • the prismatic billet obtained in Example 1 was heated at 110°C and uniaxially drawn at a draw ratio of 2.5.
  • the thus drawn molding was cut out in a direction at 0°, 45° or 90° using the uniaxially drawn direction as 0°, thereby preparing a rectangular plate of 30 mm in length x 5 mm in width x 1.5 mm in thickness, and each plate was subjected to bending strength test and repeated bending strength test in the same manner as described in Example 1.
  • Results of the bending strength test are shown in the following Table 1, and results of the repeated bending strength test are comparatively shown in the graph of Fig. 7 (cut out direction: 0°), the graph of Fig. 8 (cut out direction: 45°) and the graph of Fig.
  • each of the plates of Example 1 is a plate which maintains a strength higher than the bending strength of biological bone even against severe repeated bending deformation at room temperature (22°C) and has toughness showing no anisotropy in view of the bending strength and its retaining ratio.
  • the plate cut out at 0° maintained the strength most long but its bending strength decreased when the number of times of bending deformation exceeded 12 and reduced to about 35% of the initial bending strength by 19th bending deformation.
  • the plate cut out in the direction of 45° showed rapid reduction of the strength retaining ratio when the number of bending deformation exceeded 5 times and was broken by fatigue by the 10th bending deformation.
  • the plate cut out in the direction of 90° was broken by the 2nd bending deformation. Accordingly, the plate oriented by uniaxial drawing was a plate having no toughness, which showed not only low initial bending strength but also significant anisotropy in view of the retaining ratio of strength by repeated bending deformation.
  • a plate-shaped multi-axially oriented compression molding having a viscosity average molecular weight of 160,000 containing u-HA was obtained in the same manner as described in Example 1.
  • the thus obtained multi-axially oriented compression molding was subjected to cutting processing to cut out in a direction of 0°, 45° or 90° in the same manner as described in Example 1, thereby preparing a rectangular plate of 30 mm in length x 5 mm in width x 1.5 mm in thickness, and each plate was subjected to bending strength test and repeated bending strength test in the same manner as described in Example 1.
  • the initial bending strength of the plate cut out in the direction of 0° was 268 MPa
  • that of the plate cut out in the direction of 45° was 266 MPa
  • that of the plate cut out in the direction of 90° was 262 MPa, each of which showing higher bending strength than that of biological bone (200 MPa)
  • difference in the bending strength was hardly found by the cut out direction.
  • bending strength of the plate cut out in any direction was decreased to about 80% of its initial bending strength by the 1st to 5th bending deformation but was not substantially decreased thereafter, the strength retaining ratio was about 75% at the time of the 20th bending deformation, and breakage of the plate did not occur.
  • each of the plates comprises a multi-axially oriented compression molding containing a bioceramics powder is also a plate which has toughness and does not show anisotropy in view of the bending strength and its retaining ratio.
  • deformation restoration was not found at 37°C.
  • This billet was forged at 110°C by press-charging it into the cavity of a forming mold of 5 mm in height x 20 mm in width x 300 mm in length, thereby obtaining a molding.
  • This molding was again subjected to the forging molding by changing its mechanical direction (MD) to obtain a plate-shaped multi-axially orientated compression molding of 300 mm in length x 45 mm in width x 2.5 mm in thickness.
  • a prism of 2.5 mm in height x 2.5 mm in width x 300 mm in length was prepared by cutting the plate-shaped molding, and a wire having a circular section of 1.5 mm ⁇ was prepared by cutting corners of the prism.
  • the PLLA wire retained its initial bending strength by the 800th bending deformation and was not broken. Accordingly, it is evident that the PLLA wire is a wire having stronger toughness than the kirschner wire, which can retain its strength even against severe repeated bending deformation at room temperature (22°C).
  • a wire having a diameter of 1 mm prepared as described above was bent until the bending angle became 90° downward or upward.
  • One hundred X Ray photographs at the bent part were taken to analyze the change of microcrystalline orientation with extremely high accuracy.
  • the result shown above means that bending the wire at ordinary temperature causes the orientation direction change of the crystal chains oriented along many axes or clusters thereof, and the change occurs with a distribution.
  • the microcrystalline distribution changes from a place to a place based on the stress relaxation accompanying the deformation by the outer force at ordinary temperature.
  • the orientation of microcrystals that followed the deformation supports the strength along with the direction of deformation and the orientation of crystals that remained intact supports the original strength before deformation.
  • Example 2 Using the billet obtained in Example 1, a molding (plate) forged one time in the direction of MD1 and a molding (plate) further forged in the direction of TD direction (i.e., MD2) were prepared. The state of crystal orientation of these moldings were analyzed by the X ray diffraction method (analysis by the X ray transmission photography using a wide X ray flat camera). Several samples were layered to measure a wide range of intensity and about ten X ray photographs were taken for each of the place in order to achieve accurate analysis. The deformation ratio of the first and second forgings was 2.5, respectively. MD1 and MD2 forms an angle of 90°, i.e., in the relation of MD and TD. Representative photographs are shown as Fig. 12A, 12B, 13A, and 13B.
  • Fig. 12A is an X ray photograph of the molding forged one time, when the incident angle of the X ray was parallel to the mechanical direction MD1.
  • the diffraction of axis a and axis b draws a circle but the intensity is not symmetric about the meridian (confirmed by the measurement using a slanted sample), which indicates that the orientation of paracrystals was slanted at an angle of 10° toward the operation axis.
  • the angle of the tapered part of the forming mold for the forging was 15°.
  • Fig. 12B is an X ray photograph of the molding forged one time, when the incident angle of the X ray was right to the mechanical direction MD1.
  • the photograph shows developed layered lines and remarkable spots appeared asymmetrically about the equator. The results support that the molecular chains were slanted toward the operation axis.
  • Fig. 13A is an X ray photograph of the molding forged two times according to the present invention, when the incident angle of the X ray was parallel to the mechanical direction MD2 (i.e., right to the plate surface).
  • Fig. 13B is an X ray photograph of the molding forged two times according to the present invention, when the incident angle of the X ray was right to the mechanical direction MD2 (i.e., parallel, to the plate surface).
  • a part layered in the thickness direction was found at the center part of the plate.
  • the biodegradable and bioabsorbable implant device of the present invention exerts many remarkable effects, for example, because it has high mechanical strength and its shape after deformation such as bending and twisting within ordinary temperature range can be fixed and maintained, its shape can be easily adjusted at the site of operation, since it has substantially no anisotropy in view of strength, it does not cause whitening, breakage and sharp decrease in strength (deterioration) when its bending deformation is repeated in any direction and it has toughness, and the implant material for osteosynthesis use which contains a bioceramics powder can bind to bones and fix the fractured bone parts without loosening within a short period of time.
  • the shape-adjusting method of the present invention is a method by which shapes of the implant material can be easily adjusted due to the employment of a means that overturns common knowledge on the deformation of plastics, namely a means to carry out bending deformation and torsional deformation within ordinary temperature range, so that the troublesome prior art deformation by heating at a high temperature can be avoided.

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  • Health & Medical Sciences (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Engineering & Computer Science (AREA)
  • Surgery (AREA)
  • Mechanical Engineering (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biomedical Technology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Neurology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Medical Informatics (AREA)
  • Molecular Biology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Materials For Medical Uses (AREA)
  • Surgical Instruments (AREA)
EP99117914A 1998-09-14 1999-09-14 Resorbierbares, verformbares Implantationsmaterial Expired - Lifetime EP0987033B1 (de)

Applications Claiming Priority (2)

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JP27938998 1998-09-14
JP27938998A JP3418350B2 (ja) 1998-09-14 1998-09-14 生体内分解吸収性インプラント材とその形状調整方法

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EP2489494A1 (de) * 2011-02-17 2012-08-22 Evonik Degussa GmbH Verfahren zur Herstellung von Stäben und ihre Verwendung als Implantate
EP2747799A4 (de) * 2011-08-26 2016-01-06 Bioretec Oy Bioabsorbierbares, orientiertes und verformbares fixierungsmaterial und platte damit

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US20060142765A9 (en) * 2001-10-15 2006-06-29 Dixon Robert A Vertebral implant for bone fixation or interbody use
US8016865B2 (en) 2003-09-29 2011-09-13 Depuy Mitek, Inc. Method of performing anterior cruciate ligament reconstruction using biodegradable interference screw
US6972025B2 (en) * 2003-11-18 2005-12-06 Scimed Life Systems, Inc. Intravascular filter with bioabsorbable centering element
US7378144B2 (en) * 2004-02-17 2008-05-27 Kensey Nash Corporation Oriented polymer implantable device and process for making same
US20100191292A1 (en) * 2004-02-17 2010-07-29 Demeo Joseph Oriented polymer implantable device and process for making same
US7717946B2 (en) * 2004-06-07 2010-05-18 Degima Gmbh Polymeric plate bendable without thermal energy and methods of manufacture
US8747879B2 (en) * 2006-04-28 2014-06-10 Advanced Cardiovascular Systems, Inc. Method of fabricating an implantable medical device to reduce chance of late inflammatory response
US7150929B2 (en) * 2004-12-29 2006-12-19 Utc Fuel Cells, Llc Fuel cell coolers with inverse flow and condensation zone
US8128670B2 (en) 2005-04-15 2012-03-06 Biodynamics Llc Surgical expansion fasteners
US7833253B2 (en) 2006-01-17 2010-11-16 Biodynamics Llc Craniotomy closures and plugs
US8637064B2 (en) * 2006-09-20 2014-01-28 Warsaw Orthopedic, Inc. Compression molding method for making biomaterial composites
EP2078052B1 (de) * 2006-10-31 2010-07-28 Surmodics Pharmaceuticals, Inc. Kugelförmige polymer-teilchen
US8870871B2 (en) 2007-01-17 2014-10-28 University Of Massachusetts Lowell Biodegradable bone plates and bonding systems
US8328807B2 (en) 2008-07-09 2012-12-11 Icon Orthopaedic Concepts, Llc Ankle arthrodesis nail and outrigger assembly
US8414584B2 (en) 2008-07-09 2013-04-09 Icon Orthopaedic Concepts, Llc Ankle arthrodesis nail and outrigger assembly
US9107712B2 (en) * 2008-09-15 2015-08-18 Biomet C.V. Bone plate system for hand fractures and other small bones
JP5067957B2 (ja) * 2010-10-21 2012-11-07 保夫 敷波 相補的に強化された強化複合体及びその製造方法
CA2837568A1 (en) 2011-05-03 2012-11-08 Biodynamics, Llc Craniotomy plugs
US9381112B1 (en) 2011-10-06 2016-07-05 William Eric Sponsell Bleb drainage device, ophthalmological product and methods
US8632489B1 (en) 2011-12-22 2014-01-21 A. Mateen Ahmed Implantable medical assembly and methods
US10548649B2 (en) * 2015-04-24 2020-02-04 Biomet Manufacturing, Llc Clavicle implants
WO2023085236A1 (ja) * 2021-11-10 2023-05-19 グンゼ株式会社 骨接合材料及び骨接合材料の製造方法

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EP1857066A2 (de) 2006-05-05 2007-11-21 Bioretec Oy Bioabsorbierbares und verformbares Fixierungsmaterial und -implantat
US8080043B2 (en) 2006-05-05 2011-12-20 Bioretec Oy Bioabsorbable, deformable fixation material and implant
EP2489494A1 (de) * 2011-02-17 2012-08-22 Evonik Degussa GmbH Verfahren zur Herstellung von Stäben und ihre Verwendung als Implantate
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EP2747799A4 (de) * 2011-08-26 2016-01-06 Bioretec Oy Bioabsorbierbares, orientiertes und verformbares fixierungsmaterial und platte damit

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US6632503B1 (en) 2003-10-14
US6908582B2 (en) 2005-06-21
DE69908520D1 (de) 2003-07-10
US20030006533A1 (en) 2003-01-09
JP3418350B2 (ja) 2003-06-23
AU4757699A (en) 2000-03-23
CA2282132C (en) 2009-07-14
ES2200447T3 (es) 2004-03-01
JP2000084064A (ja) 2000-03-28
DE69908520T2 (de) 2004-05-06
CA2282132A1 (en) 2000-03-14
EP0987033B1 (de) 2003-06-04
AU759061B2 (en) 2003-04-03
ATE242016T1 (de) 2003-06-15

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